Role Of IP3 Receptors Research Articles

The ER-mitochondria Ca2+ signaling in cancer progression: Fueling the monster.

Cancer is a leading cause of death worldwide. All major tumor suppressors and oncogenes are now recognized to have fundamental connections with metabolic pathways. A hallmark feature of cancer cells is a reprogramming of their metabolism even when nutrients are available. Increasing evidence indicates that most cancer cells rely on mitochondrial metabolism to sustain their energetic and biosynthetic demands. Mitochondria are functionally and physically coupled to the endoplasmic reticulum (ER), the major calcium (Ca2+) storage organelle in mammalian cells, through special domains known as mitochondria-ER contact sites (MERCS). In this domain, the release of Ca2+ from the ER is mainly regulated by inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), a family of Ca2+ release channels activated by the ligand IP3. IP3R mediated Ca2+ release is transferred to mitochondria through the mitochondrial Ca2+ uniporter (MCU). Once in the mitochondrial matrix, Ca2+ activates several proteins that stimulate mitochondrial performance. The role of IP3R and MCU in cancer, as well as the other proteins that enable the Ca2+ communication between these two organelles is just beginning to be understood. Here, we describe the function of the main players of the ER mitochondrial Ca2+ communication and discuss how this particular signal may contribute to the rise and development of cancer traits.

Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review.

This article addresses the disparity in the transduction pathways for hypoxic and hypercapnic stimuli in carotid body glomus cells. We investigated and reviewed the experimental evidence showing that the response to hypoxia, but not to hypercapnia, is mediated by 1,4,5-inositol triphosphate receptors (IP3R/s) regulating the intracellular calcium content [Ca2+]c in glomus cells. The rationale was based on the past observations that inhibition of oxidative phosphorylation leads to the explicit inhibition of the hypoxic chemoreflex. [Ca2+]c changes were measured using cellular Ca2+-sensitive fluorescent probes, and carotid sinus nerve (CSN) sensory discharge was recorded with bipolar electrodes in in vitro perfused-superfused rat carotid body preparations. The cell-permeant, 2-amino-ethoxy-diphenyl-borate (2-APB; 100μM) and curcumin (50μM) were used as the inhibitors of IP3R/s. These agents suppressed the [Ca2+]c, and CSN discharge increases in hypoxia but not in hypercapnia, leading to the conclusion that only the hypoxic effects were mediated via modulation of IP3R/s. The ATP-induced Ca2+ release from intracellular stores in a Ca2+-free medium was blocked with 2-APB, supporting this conclusion.

The Role of IP3 Receptors in Generating Calcium Waves and Cerebral Myogenic Tone

This study of the cerebral vasculature examined whether: 1) elevated intravascular pressure induces asynchronous Ca2+ waves by activating IP3 receptors; and 2) these events drive myogenic tone development by augmenting myosin light chain phosphorylation (LC20). Rat cerebral arteries pressurized between 20–100 mmHg were examined in the absence and presence of agents that deplete the sarcoplasmic reticulum (SR) of Ca2+ or block IP3 receptors. Diameter and membrane potential (VM) were assessed using conventional techniques whereas Ca2+ waves and LC20 phosphorylation were monitored using confocal microscopy and western blot analysis, respectively. Elevated intravascular pressure increased the proportion of smooth muscle cells firing Ca2+ waves as well as the frequency of these voltage‐independent events. Agents that deplete the SR of Ca2+ (ryanodine, CPA and Thapsigargin) or block IP3 receptors (2‐APB or Xestospongin‐C) eliminated Ca2+ wave generation. The loss of Ca2+ waves attenuated LC20 phosphorylation and attenuated myogenic tone development. It did not, however, alter pressure‐induced depolarization in an intact artery In summary, this study shows that pressure‐induced Ca2+ waves facilitate cerebral myogenic tone by providing a proportion of the Ca2+ required to activate myosin light chain kinase. Supported by NSERC.

Role of IP3 receptor and its associated proteins in Ca2+ signaling

Role of IP3 receptor and its associated proteins in Ca2+ signaling